Pulsatile secretion of GnRH by hypothalamic neurons results in gonadotropin secretion and release and hence plays a critical role in the regulation of normal reproductive function and cyclicity in women. The central mechanisms that regulate neuronal function are not understood. Chronic nutritional deprivation in people and primates causes hypothalamic dysfunction and hypogonadism, but is not a clinically acceptable model. Recent indicates that acute food deprivation in men and male monkeys decreases gonadotropin pulse frequency and testosterone levels. We hypothesize that acute fasting may inhibit the female reproductive axis in a similar way, and may serve as a tool to study the regulation of the GnRH pulse generator. Short-term fasting, common among women, might thus inhibit the reproductive axis and diminish fertility. To study the effects of nutritional deprivation on GnRH neuronal function, we have fasted women completely for three days during the follicular phase of the menstrual cycle. Preliminary data show that this reversible blunts follicular growth but does not decrease gonadotropin pulsatility, suggesting that even a 3 day fast can affect follicular development, primarily at the ovary, and that species-specific and sex- specific differences exist in the activity of the GnRH pulse generator during a fast. We have also used the GT1-7 neuronal cell line to study the regulation of GnRH secretion in vitro. This line is derived from a transgenic mouse transfected with the sequences for the rat GnRH promoter and the SV 40 T antigen. We have shown that neuronal survival and GnRH secretion by these cells is affected by the glucose and IGF-1 concentrations in the media, so that glucose-free media and supra- physiologic concentrations of IGF-I increase cell death, While physiologic concentration of IGF-1 protects the neurons from hypoglycemia damage. GnRH secretion is inhibited by IGF-1, 1-100 ng/mL. These data suggest that the hypogonadism of starvation may be modulated directly at the level of the GnRH neuron by the availability of nutrients and growth factors.